This application, a joint effort of 26 centers of the NAPRTCS, is entitled Chronic Renal Insufficiency (CRI) in NAPRTCS Patients. We will enroll 300 children (1-16 years) with measured glomerular filtration rates (GFR) of 25-75 mL/min/1.73m2. Follow-up with annual GFR and 6 month physical examinations and determinations of hemoglobin, electrolytes, serum, albumin, serum calcium, serum phosphorus, parathyroid hormone and urinary indices will test the 1st hypothesis that this cohort will most accurately define the rate of and the risk factors for progression of CRI, and that this progression will be correlated with proteinuria, albumin, blood pressure, nutritional status, growth and hyperparathyroidism. To test the 2nd hypothesis that cardiovascular disease develops in children with mild CRI and that its orevalence and severity increase in association with the progression of CRI, we will perform baseline and annual 24-hour ambulatory blood pressure monitoring, echocardiographic assessments to determine left-ventricularmass and LV function, and B-mode ultrasound of the carotid artery to determine the IMT and carotid artery compliance. To test the 3rd hypothesis that the neurocognitive outcome of children with CRI is influenced by the progression of renal insufficiency, a battery of validated neurocognitive tests will be conducted at study entry and at 6, 12 and 24 months to assess many cortical and subcortical areas of brain function. To test the 4th hypothesis that chronic inflammation contributes to cachexia, growth hormone resistance and growth retardation, we will examine the impact of circulating cytokine and neuropeptide concentrations on dietary intake, nutritional and growth parameters as well as growth hormone axis pertubations and responsiveness to growth hormone therapy. Finally, to test the 5th hypothesis that a correlation exist between bone histology, serum concentration of PTH and measured GFR, we will measure and characterize the biochemical and histologic features of renal osteodystrophy and determine the serum concentrations of PTH that are associated with normal rates of bone formation.